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11-04-2010 | Cardiometabolic | Article

KIF6 gene gene variant influenced pravastatin efficacy in CARE trial

Abstract

Free abstract

MedWire News: A variant in the gene encoding kinesin family member 6 (KIF6) influences the rate of coronary events during pravastatin treatment, a substudy of the Cholesterol and Recurrent Events (CARE) trial has found.

The analysis showed that pravastatin therapy markedly reduced fatal and nonfatal coronary events in carriers of the KIF6 719Arg allele, irrespective of their ethnicity, whereas pravastatin had no such benefit in noncarriers.

“The putative cargo of the KIF6 protein and how it is involved in modulating coronary artery disease risk and response to statin therapy is unknown,” admit the investigators writing in the American Journal of Cardiology.

CARE was a double-blind trial involving 4159 patients with myocardial infarction (MI) who were randomly assigned to pravastatin 40 mg/day or placebo. A genetic substudy involving 3103 patients previously demonstrated that Caucasian participants with the KIF6 719Arg variant had a lower risk for fatal/nonfatal MI than noncarriers.

In this new, expanded genetic analysis, Dov Shiffman (Celera, Alameda, California) and team examined the influence of the KIF6 genotype on risk for the primary endpoint (fatal coronary events or nonfatal MI) among all ethnic groups in CARE.

The overall frequency of the 719Arg variant was 60%, but it varied by ethnicity, being highest (89.7%) among African Americans, moderate among Hispanics (72.9%) and Asian/Pacific Islanders (66.7%), and lowest among Caucasians (59.2%). The prevalence of coronary artery disease (CAD) risk factors was similar in 719Arg carriers and noncarriers.

Using Cox regression models that adjusted for age, gender, and self-reported ethnicity, pravastatin therapy reduced the primary endpoint in KIF6 719Arg carriers (hazard ratio [HR]=0.63) but not in noncarriers (HR=1.01).

After further adjustment for CAD risk factors and principal components of genetic variability, pravastatin again reduced events in carriers (HR=0.64), but not in noncarriers (HR=0.90).

Admitting that the mechanisms underlying these effects are unknown, the researchers conclude: “KIF6 ribonucleic acid is expressed in coronary arteries at a higher level than in human umbilical vein endothelial cells, so investigation of KIF6 protein expression in different stages of atherosclerotic plaque should suggest cell- or stage-specific roles for KIF6 involvement in CAD.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Joanna Lyford